We employ several approaches to attempting to understand the etiology and pathogenesis of multiple sclerosis. We will continue attempts to recover a virus or identify virus antigen in brain tissue of patients with MS. We will use human tissues in culture and animal model systems in vivo and in vitro to study the behavior of known neurotropic viruses, virus latency, and attempt to improve virus detection systems. We will study immunologic alterations associated with MS, with particular attention to compartmentalization of the immune response within the nervous system as compared with non-nervous system tissues. We will continue to focus on the oligodendrocyte as a possible target cell in MS, and employ isolated oligodendrocytes for immunologic and virologic studies related to MS.